The invention relates to a process for the production of 6.alpha.,9.alpha.-difluoro-11.beta.,17.alpha.-dihydroxy-16.alpha.-methyl-4 -pregnene-3,20-dione and its derivatives of general formula ##STR2## wherein symbolizes a single bond or a double bond and
X represents a hydrogen atom, a bromine atom, an iodine atom or an alkanoyloxy group with a maximum of 8 carbon PA1 X is H, Br, I or alkanoyloxy of 1-8 carbon atoms, comprising reacting a 3.beta.,17.alpha.-dihydroxy-16.alpha.-methyl-5-pregnen-20-one of formula II ##STR4## with an N-bromoacylamide and hydrogen fluoride in the presence of urea, oxidizing the resultant 5.alpha.-bromo-6.beta.-fluoro-3.beta.,17.alpha.-dihydroxy-16.alpha.-methyl -pregnan-20-one of formula III ##STR5## by means of chromic acid, splitting off hydrogen bromide (dehydrobrominating) from the formed 5.alpha.-bromo-6.beta.-fluoro-17.alpha.-hydroxy-16.alpha.-methyl-pregnane- 3,20-dione of formula IV ##STR6## hydroxylating the thus-produced 6.alpha.-fluoro-17.alpha.-hydroxy-16.alpha.-methyl-4-pregnene-3,20-dione of formula V at the 11-position ##STR7## by means of a live culture of Curvularia lunata splitting off water (dehydrating) from the resultant 6.alpha.-fluoro-11.beta.,17.alpha.-dihydroxy-16.alpha.-methyl-4-pregnene-3 ,20-dione of formula VI ##STR8## adding BrOH to the resultant 6.alpha.-fluoro-17.alpha.-hydroxy-16.alpha.-methyl-4,9,(11)-pregnadiene-3, 20-dione of formula VII ##STR9## splitting off hydrogen bromide from the resultant 9.alpha.-bromo-6.alpha.-fluoro-11.beta.,17.alpha.-dihydroxy-16.alpha.-meth yl-4-pregnene-3,20-dione of formula VIII ##STR10## opening the epoxide ring of the resultant 9,11.beta.-epoxy-6.alpha.-fluoro-17.alpha.-hydroxy-16.alpha.-methyl-4-preg nene-3,20-dione of formula IX ##STR11## by means of hydrogen fluoride to form 6.alpha., 9.alpha.-difluoro-11.beta., 17.alpha.-dihydroxy-16.alpha.-methyl-4-pregnen e-3, 20-dione of formula Ia ##STR12## Optionally, the thus-produced pregnene derivative is dehydrogenated by fermentation with microorganisms capable of steroid delta.sup.1 dehydrogenation, to form 6.alpha.,9.alpha.-difluoro-11.beta., 17.alpha.-dihydroxy-16.alpha. -methyl-1,4-pregnadiene-3,20-dione of formula Ib ##STR13## In addition, the formed 1,4-pregnadiene-3,20-dione can, optionally, be halogenated to 6.alpha.,9.alpha.-difluoro-11.beta.,17.alpha.-dihydroxy-21-halogen-16.alph a.-methyl-1,4-pregnadiene-3,20-dione of formula Ic ##STR14## wherein X represents a bromine atom or iodine atom, PA1 by means of bromine or iodine. PA1 by exchanging iodine or bromine for an alkanoyloxy group.
Pregnene derivatives of formula I are useful as intermediates for production of the corticoid, flumethasone, i.e., 6.alpha.,9.alpha.-difluoro-11.beta.,17.alpha., 21-trihydroxy-16.alpha.-methyl-1,4-pregnadiene-3,20-dione. Flumethasone is a known corticoid active ingredient. However, synthesis of flumethasone is very expensive (J. A. Edwards et al., J. Amer. Chem. Soc., 82,1960, 2318-2322).